Elevated levels of soluble CD44 are associated with advanced disease and in vitro proliferation of neoplastic lymphocytes in B-cell chronic lymphocytic leukaemia

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Item Type:	Article
Title:	Elevated levels of soluble CD44 are associated with advanced disease and in vitro proliferation of neoplastic lymphocytes in B-cell chronic lymphocytic leukaemia
Creators Name:	Eisterer, W., Bechter, O., Soederberg, O., Nilsson, K., Terol, M., Greil, R., Thaler, J., Herold, M., Finke, L., Guenthert, U., Montserrat, E. and Stauder, R.
Abstract:	Purpose: Increased expression of the adhesion molecule CD44 has been associated with an unfavourable clinical outcome in lymphomas. We evaluated the prognostic value of soluble CD44 in B-cell chronic lymphocytic leukaemia (B-CLL) and analysed the source and regulation of CD44 secretion in B-CLL clones in vitro. Patients and methods: Levels of soluble CD44 standard (sCD44s) and of the soluble variant isoform CD44v6 (sCD44v6) were analysed by enzyme linked immuno sorbent assay. Highly purified B-CLL cells (98% CD19+CD3- cells) were stimulated in vitro by different combinations of thioredoxin (Trx), Staphylococcus aureus Cowan strain 1 (SAC), IL-2, IL-4, IL-10, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and by anti-CD40 mAbs presented on irradiated CD32L cells. Results: Serum levels of sCD44s and of sCD44v6 are significantly elevated in B-CLL patients (n=90) in comparison with normal persons (n=44) (P<0.001). Elevated levels of sCD44s and sCD44v6 are associated with an advanced disease as reflected by an extended lymph node involvement (P<0.02), an advanced Binet (P<0.03) and Rai stage (P<0.04) and chemotherapy requirement (P<0.02). High levels of sCD44s are associated with high leukocyte counts (P<0.04) and increased sCD44v6 is significantly associated with splenomegaly (P<0.002). In B-CLL sCD44s as well as sCD44v6 is shed from leukaemia cells as shown by in vitro cultures. Stimulation of B-CLL clones results in a proliferation-associated increased secretion of sCD44s (rho=0.7; P=0.0001) and of sCD44v6 (rho=0.5; P=0.005). B-CLL clones from advanced stage patients are characterised by an increased capacity for proliferation and CD44 production in comparison with early stage patients. Conclusions: Both sCD44s and sCD44v6 represent a reliable prognostic marker in B-CLL and may be involved in the pathogenesis of B-CLL.
Keywords:	B-Cell Chronic Lymphocytic Leukaemia, B-CLL, CD44, CD44 Variant Isoforms, CD44v, HA, HEV, High-Endothelial Venules, Hyaluronate, NHL, Non-Hodgkin's Lymphoma, Prognosis, SCD44s, SCD44v6, Serum Marker, Soluble CD44s, Soluble CD44v6
Source:	Leukemia Research
ISSN:	0145-2126
Publisher:	Elsevier / Pergamon Press
Volume:	28
Number:	10
Page Range:	1043-1051
Date:	1 January 2004
Official Publication:	https://doi.org/10.1016/j.leukres.2004.01.016
PubMed:	View item in PubMed

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